Tonix Pharmaceuticals Announces Topline Results from Phase 2 Proof-of-Concept Study of TNX-601 ER for the Treatment of Major Depressive Disorder The study did not achieve statistical significance on the primary endpoint

Tonix Pharmaceuticals Holding Corp. 8-K

Tonix Pharmaceuticals Announces Topline

Results from Phase 2 Proof-of-Concept Study of TNX-601 ER for the Treatment of Major Depressive Disorder

The study did not achieve statistical significance

on the primary endpoint

Tonix is discontinuing

development of TNX-601 ER based on the efficacy results of this study

Tonix expects topline data results in December

2023 for its Phase 2 study of TNX-1900 in chronic migraine and Phase 3 study of TNX-102 SL in fibromyalgia

CHATHAM, N.J., October 31, 2023 -

Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a biopharmaceutical company with marketed products and a pipeline of development candidates,

today announced topline results from the Phase 2 proof-of-concept double-blind, randomized, multi-center, placebo-controlled UPLIFT study

of TNX-601 ER* (tianeptine hemioxalate extended-release tablets) in patients with major depressive disorder (MDD). The primary efficacy

endpoint of change from baseline in depression severity, as measured by the Montgomery- sberg Depression Rating Scale (MADRS) total

score, did not achieve clinical or statistical significance.

efficacy results, we are discontinuing development of TNX-601 ER. We look forward to topline results from our Phase 2 study of TNX-1900

in chronic migraine in early December and topline results from our Phase 3 potential NDA-enabling study of TNX-102 SL in fibromyalgia

in late December," said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. "We would like

to thank the patients, their families, and all the investigators and researchers who participated in the Phase 2 UPLIFT study."

In the Phase 2 UPLIFT study, TNX-601 ER

was orally administered as monotherapy once a day to 132 patients who, upon entering the study, met a DSM-5 diagnosis of moderate-to-severe

depression with a duration for the current major depressive episode of at least 12 weeks. Efficacy was assessed using the MADRS to measure

any potential change in patients' depression severity from baseline. In the study, TNX-601 ER was generally well-tolerated with

a favorable safety profile. There was one serious adverse event (SAE) experienced in the placebo group, and two SAEs in the active treatment

group deemed possibly related to study drug, both of which resolved without sequelae.

About the Phase 2 UPLIFT Study

The Phase 2 proof-of-concept UPLIFT study,

TNX-TI-M201, is a double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of TNX-601 ER taken

orally once-daily for 6 weeks for the treatment of moderate-to-severe MDD. It is a parallel design study with a TNX-601 ER 39.4 mg arm

and a placebo arm. A total of 132 participants were randomized in a 1:1 ratio into the two arms across approximately 27 U.S. sites, enrolling

adult patients 18-65 years old with a DSM-5 diagnosis of MDD and a duration for the current major depressive episode of at least 12 weeks.

The primary efficacy endpoint is mean change from baseline in the MADRS total score at Week 6. Key secondary efficacy endpoints include

the Clinical Global Impression - Severity Scale (CGI-S) and the Sheehan Disability Scale (SDS).

For more information, see ClinicalTrials.gov

Identifier: NCT05686408.

About Major Depressive Disorder (Depression)

According to the National Institute of Mental

Health, an estimated 21 million adults in the U.S. in 2020 experienced at least one major depressive episode1, with highest

prevalence among individuals aged 18-25 at a rate of 17.0%. For approximately 2.5 million adults in the U.S., adjunctive therapies are

necessary for depression treatment.2,3 Depression is a condition characterized by symptoms such as a depressed mood or loss

of interest or pleasure in daily activities most of the time for two weeks or more, accompanied by appetite changes, sleep disturbances,

motor restlessness or retardation, loss of energy, feelings of worthlessness or excessive guilt, poor concentration, and suicidal thoughts

and behaviors. These symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of

functioning. The majority of people who suffer from depression do not respond adequately to initial antidepressant therapy.4

1 Data Courtesy of SAMHSA on Past

Year Prevalence of Major Depressive Episode Among U.S. Adults 2020. Retrieved from http://www.nimh.nih.gov/health/statistics/major-depression.shtml

2 IMS NSP, NPA, NDTI MAT-24-month

data through Aug 2017.

3 Kubitz N, et al. PLoS One 2013,

4 Rush AJ, et al. Am J. Psychiatry

2007, 163 (11), 1905-1917.

TNX-601 ER (tianeptine hemioxalate extended-release

tablets) is a novel oral formulation of tianeptine designed for once-daily daytime dosing in development as a candidate for the treatment

of MDD. Tianeptine sodium (amorphous) immediate release (dosed 3 times daily) was first marketed for depression in France in 1989 and

has been available for decades in Europe, Russia, Asia, and Latin America for the treatment of depression. Tianeptine sodium has an established

safety profile from decades of use in these jurisdictions. Currently no tianeptine-containing product is approved in the U.S. and no extended-release

tianeptine product is approved in any jurisdiction. Tonix discovered a novel oxalate salt of tianeptine that may provide improved stability,

consistency, and manufacturability compared to known salt forms of tianeptine.

Tonix Pharmaceuticals

Tonix is a biopharmaceutical

company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate

suffering. Tonix Medicines, our commercial subsidiary, markets Zembrace SymTouch (sumatriptan injection) 3 mg and Tosymra

(sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were

acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in

adults. Tonix's development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease

product candidates. Tonix's CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric

and addiction conditions. Tonix's lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase

3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third

quarter of 2023, with topline data expected in late December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long

COVID, a chronic post-acute COVID-19 condition, and topline results were reported in the third quarter of 2023. TNX-1900 (intranasal potentiated

oxytocin), is in development as a preventive treatment in chronic migraine, and enrollment has completed in a Phase 2 proof-of-concept

study with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity and

social anxiety disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed

to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected

to be initiated in the fourth quarter of 2023. Tonix's rare disease development portfolio includes TNX-2900 (intranasal potentiated

oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix's immunology

development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is

a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for

the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix's infectious

disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine

platform or recombinant pox vaccine platform for other infectious diseases, including

TNX-1800, in development as a vaccine to protect against COVID-19 . The infectious disease development portfolio also includes TNX-3900

and TNX-4000, which are classes of broad-spectrum small molecule oral antivirals.

*Tonix's product development candidates are

investigational new drugs or biologics and have not been approved for any indication.

Zembrace SymTouch and Tosymra are registered trademarks

of Tonix Medicines. Intravail is a registered trademark of Aegis Therapeutics, LLC, a wholly owned subsidiary of Neurelis, Inc. All other

marks are property of their respective owners.

This press release and further information about

Tonix can be found at www.tonixpharma.com.

Forward Looking Statements

Certain statements in this press release are

forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the

use of forward-looking words such as "anticipate," "believe," "forecast," "estimate,"

"expect," and "intend," among others. These forward-looking statements are based on Tonix's current expectations

and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those

indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA

clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products;

risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties

of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development